Abstract
Nuclear receptors are ligand-activated transcription factors capable of regulating the expression of complex gene networks. The family includes seven subfamilies of proteins with a wide phylogenetic distribution. A novel subfamily with two DNA-binding domains (2DBDs) has been reported in Schistosoma mansoni (Platyhelminth, Trematoda). This work describes the cDNA cloning and bioinformatics analysis of Eg2DBDα, a 2DBD nuclear receptor isoform from the parasite Echinococcus granulosus (Platyhelminth, Cestoda). The Eg2DBDα gene coding domain structure was analysed. Although two additional 2DBD nuclear receptors are reported in the parasite database GeneDB, they are unlikely to be expressed in the larval stage. Phylogenetic relationships between these atypical proteins from different cestodes are also analysed including S. mansoni 2DBD nuclear receptors. The presence of two DNA binding domains confers particular interest to these nuclear receptors, not only concerning their function but to the development of new antihelminthic drugs.
Highlights
The field of nuclear receptors (NRs) has undergone an astounding evolution since the biochemical identification of the first nuclear receptor in the early of the 1960’s [1]
Three E. granulosus 2DBD nuclear receptor sequences were extracted from the GeneDB database using Mus musculus PPARα as a template, with the following accession numbers: EgrG 000379600.1 (Eg37), EgrG 00240200 (Eg24) and EgrG 000458200 (Eg45)
The cloned 5 ́ coding region overlaps 843 bp with the previously mentioned fragment. The identity of both fragments with EgrG 000379600.1 coding sequence was verified by alignment showing some differences explained below
Summary
The field of nuclear receptors (NRs) has undergone an astounding evolution since the biochemical identification of the first nuclear receptor in the early of the 1960’s [1]. NRs belong to a large protein superfamily of ligand-activated transcription factors that bind to DNA sequences. This family includes receptors for steroid hormones, thyroid hormone, vitamin D, retinoids, fatty acids and prostaglandins, which bind hydrophobic ligands and regulate a variety of mammals’ genes [2,3]. A large number of them have no defined ligand and are described as orphan receptors [2, 4,5]. Receptors of this family have been reported in insects, worms and amphibians, in addition to mammalian species [6]. NRs emerged long before the divergence of vertebrates and invertebrates, during the earliest metazoan evolution [7]
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